panobinostat (lbh589) and imatinib mesylate in treating patients with previously treated chronic phase chronic myelogenous leukemia

Conditions: Leukemia

Summary: rationale: panobinostat and imatinib mesylate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. purpose: this phase i trial is studying the side effects and best dose of panobinostat when given together with imatinib in treating patients with previously treated chronic phase chronic myelogenous leukemia.

objectives: primary * to determine the safety and tolerability of lbh589 given in combination with imatinib mesylate in cml patients who are in major cytogenetic remission (mcr) with residual bcr-abl positive cells after at least 1 year of daily imatinib mesylate treatment. * to determine the maximum tolerated dose (mtd) and dose-limiting toxicity of lbh589 given in combination with imatinib mesylate in cml patients. secondary * to study the effect of lbh589 given in combination with imatinib mesylate on cytogenetic response status and bcr-abl levels in cml patients in major cytogenetic remission on imatinib mesylate treatment. tertiary * to study the effect of lbh589 given in combination with imatinib mesylate on residual bcr-abl positive primitive progenitors in cml patients in major cytogenetic remission on imatinib mesylate treatment. outline: this is dose-escalation study of panobinostat. patients receive oral panobinostat once daily on days 1, 3 and 5; 8, 10, and 12; 15, 17, and 19; and 22, 24, and 26. patients also receive oral imatinib mesylate once daily on days 1-28. treatment repeats every 21 or 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. after completion of study treatment, patients are followed up at 1 month and then every 3 months for up to 1 year.

Eligibility criteria:
inclusion criteria: * ability to provide written informed consent obtained prior to participation in the study and any related procedures being performed * cml cp patients who have been treated with and tolerated imatinib for 1 year or more, have achieved at least major cytogenetic response and continue to be bcr-abl positive (patients should be receiving imatinib at a dose of 400 daily at the time of entry into the study) * anc and plt need to be in the normal range * serum albumin \>= 3g/dl * ast/sgot and alt/sgpt =\< 2.5 x upper limit of normal (uln) * serum bilirubin =\< 1.5 x uln * serum creatinine =\ = 50 ml/min * serum potassium \>= lower limit of normal (lln) * serum phosphorus \>= lln * serum total calcium (corrected for serum albumin) or serum ionized calcium \>= lln * serum magnesium \>= lln * ecog performance status of =\< 2 exclusion criteria: * prior treatment with an hdac inhibitor * patient who have been treated with imatinib \ 400 mg daily * impaired cardiac function including any one of the following: screening ecg with a qtc \> 450 msec; patients with congenital long qt syndrome; history or presence of sustained ventricular tachycardia; any history of ventricular fibrillation or torsades de pointes; bradycardia defined as heart rate \ = 50 beats per minute are eligible); patients with a myocardial infarction or unstable angina within 6 months of study entry; congestive heart failure (ny heart association class iii or iv); right bundle branch block and left anterior hemiblock (bifascicular block) * uncontrolled hypertension * concomitant use of drugs with a risk of prolonging the qt interval or inducing torsades de pointes * concomitant use of cyp3a4 inhibitors * patients with unresolved diarrhea \> ctcae grade 1 * impairment of gastrointestinal (gi) function or gi disease that may significantly alter the absorption of oral lbh589 * other concurrent severe and/or uncontrolled medical conditions * patients who have received chemotherapy, any investigational drug or undergone major surgery \< 4 weeks prior to starting study drug or who have not recovered from side effects of such therapy * concomitant use of any other anti-cancer therapy or radiation therapy * patients being treated with coumadin (unless patients who require anticoagulation can be switched to a low-molecular weight or standard heparin) * female patients who are pregnant or breast feeding or patients of reproductive potential not willing to use a double method of contraception including a barrier method (i.e. condom) during the study and 3 months after the end of treatment (women of childbearing potential \[wocbp\] must have a negative serum pregnancy test within 7 days of the first administration of oral lbh589) * male patients whose sexual partners are wocbp not willing to use a double method of contraception including condom during the study and 3 months after the end of treatment * patients with a history of another primary malignancy within 5 years other than curatively treated cis of the cervix, or basal or squamous cell carcinoma of the skin * patients with known positivity for human immunodeficiency virus (hiv) or hepatitis c; baseline testing for hiv and hepatitis c is not required * patients with any significant history of non-compliance to medical regimens or with inability to grant a reliable informed consent

Keywords: chronic phase chronic myelogenous leukemia